Pain contains sensory-discriminative, affective-motivational, and cognitive-evaluative dimensions. Animal studies demonstrate that social interaction/support inhibits the sensory dimension in acute pain models. However, it is yet to be demonstrated whether social interaction/support modulates the affective dimension. The objective of this proposal is to utilize a combination of behavioral, optogenetic and micro-wire array approaches to evaluate the effects and mechanisms of social support on the affective components of pain. Our preliminary data demonstrate that the presence of a cage mate during complete Freund adjuvant-induced pain- paired conditioning mitigated the avoidance response assessed with a conditioned place avoidance (CPA) test, indicating that social interaction/support alleviated the on-going pain and affective response. The data also showed that rostral anterior cingulated cortex (rACC) excitatory neuronal activity was enhanced during pain. Yellow light stimulation suppressed rACC excitatory neuronal activity and CPA in rats bearing the viral vector AAV5-CaMKIIa-eNpHR3.0-EYFP in the rACC. We hypothesize that social interaction/support alleviates affective response by inhibiting rACC neuronal activities. Aim I is to determine whether social interaction/support inhibits inflammatory pain-induced affective response. We hypothesize that a same- or opposite-sex cage mate-provided social interaction/support will inhibit pain-induced affective response and that untreated cage mates will show CPA. Aim II is to determine whether social interaction/support inhibits rACC excitatory neuronal activity. The rACC will be stimulated with blue or yellow light through optical fibers, an multi-channel electrodes will record neuronal activity during pre-conditioning test, conditioning and post- conditioning test in both CFA-injected and cage mate rats. Multiunit activities will be sorted to identify individual neuronal spike. We hypothesize that 1) social interaction/support wil significantly inhibit rACC excitatory neuronal activity in CFA-injected rats, 2) blue light stimulation of the hChR2-bearing rACC during pain-paired conditioning will counteract the effect of social interaction/support, and yellow light stimulation of the eNpHR3.0-bearing rACC will significantly inhibit affective pain, 3) cage mates will show enhanced rACC neuronal activity compared to baseline when in pain-paired box during both conditioning and post conditioning- test and, 4) blue light and yellow light stimulation during pain-paired conditioning will respectively facilitate and decrease CPA of cage mates compared to control. The findings will advance knowledge of the effects and mechanisms of a non-pharmacological therapy on persistent pain. RELEVANCE: Control and management of pain remain serious challenges. The findings of this proposed study will advance knowledge of the effects and mechanisms of a non-pharmacological therapy for pain.